title: Intraperoxisomal redox balance in mammalian cells: oxidative stress and interorganellar cross-talk.
abstract: Reactive oxygen species (ROS) are at once unsought by-products of metabolism and critical regulators of multiple intracellular signaling cascades. In nonphotosynthetic eukaryotic cells, mitochondria are well-investigated major sites of ROS generation and related signal initiation. Peroxisomes are also capable of ROS generation, but their contribution to cellular oxidation-reduction (redox) balance and signaling events are far less well understood. In this study, we use a redox-sensitive variant of enhanced green fluorescent protein (roGFP2-PTS1) to monitor the state of the peroxisomal matrix in mammalian cells. We show that intraperoxisomal redox status is strongly influenced by environmental growth conditions. Furthermore, disturbances in peroxisomal redox balance, although not necessarily correlated with the age of the organelle, may trigger its degradation. We also demonstrate that the mitochondrial redox balance is perturbed in catalase-deficient cells and upon generation of excess ROS inside peroxisomes. Peroxisomes are found to resist oxidative stress generated elsewhere in the cell but are affected when the burden originates within the organelle. These results suggest a potential broader role for the peroxisome in cellular aging and the initiation of age-related degenerative disease.
authors.affiliation: Laboratory of Lipid Biochemistry and Protein Interactions, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Oksana
authors.initials: O
authors.lastname: Ivashchenko
authors.forename: Paul P
authors.initials: PP
authors.lastname: Van Veldhoven
authors.forename: Chantal
authors.initials: C
authors.lastname: Brees
authors.forename: Ye-Shih
authors.initials: YS
authors.lastname: Ho
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Terlecky
authors.forename: Marc
authors.initials: M
authors.lastname: Fransen
mesh_terms: D000818:Animals; D019556:COS Cells; D002374:Catalase; D002460:Cell Line; D016922:Cellular Senescence; D002522:Chlorocebus aethiops; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D015388:Organelles / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020675:Peroxisomes / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D002374:Catalase